Chronic BronchitisPhase 2NCT04441788
A Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Participants With Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD) With Chronic Bronchitis (CB)
A Phase 2 study testing ION-827359 in people with Chronic Bronchitis and Chronic Obstructive Pulmonary Disease, run by Ionis Pharmaceuticals, Inc. at 15 sites in 4 countries.
Trial summary
The purpose of this study was to evaluate the effect of ION-827359 on forced expiratory volume in 1 second (FEV1) in participants with mild to moderate COPD with CB. Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- Chronic Bronchitis, Chronic Obstructive Pulmonary Disease
- What is being tested?
- ION-827359
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 15 sitesin 4 countries
- Study dates
- 22 Dec 2020to 9 Aug 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements
- Males or females. Aged 40-70 inclusive at the time of informed consent
- Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or postmenopausal
- BMI < 35.0 kg/m^2
- Participants with a diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS)
- Ability to perform acceptable and reproducible spirometry
Show all 12Show fewer
- Post-bronchodilator (4 puffs of albuterol) spirometry at Screening demonstrating the following:
- FEV1/ forced vital capacity (FVC) ratio of < 0.70 ii. FEV1 ≥ 50% and ≤ 90% of predicted normal
- Clinically stable COPD in the 4 weeks prior to Screening (Visit 1)
- Current and former smokers with smoking history of ≥ 20 pack years
- Meet SGRQ definition of CB
- CAT score ≥ 10
Who cannot join
- Clinically significant abnormalities in medical history (e.g., previous acute coronary syndrome within 6 months of screening, congestive heart failure, major surgery within 3 months of Screening) or physical examination
- Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a subject unsuitable for inclusion
- Urine protein/creatinine (P/C) ratio ≥ 0.3 mg/mg. In the event of P/C ratio above this threshold eligibility may be confirmed by a quantitative total urine protein measurement of < 300 mg/24 hr
- Positive test (including trace) for blood on urinalysis. In the event of a positive test eligibility may be confirmed with urine microscopy showing ≤ 5 red blood cells per high power field
- alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, alkaline phosphatase (ALP), serum creatinine, blood urea nitrogen (BUN) > 1.5 × upper limit of normal (ULN)
- Platelet count < LLN
Show all 19Show fewer
- Serum potassium > 5.2 mmol/L
- Estimated GFR < 60 mL/min (as determined by the Cockcroft-Gault Equation for creatinine clearance)
- A positive PCR test for SARS-CoV-2 at any time prior to randomization
- Any active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to first day Study Drug product is administered to the participant (Study Day 1)
- Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
- Clinically important pulmonary disease other than COPD
- Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA) guidelines (GINA 2011) or other accepted guidelines. Participants with a past medical history of asthma (e.g. childhood or adolescence) may be included
- Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 4 weeks prior to enrolment (Visit 1)
- Acute upper or lower respiratory infection requiring antibiotics or antiviral medication within 4 weeks prior to enrolment (Visit 1)
- Long term oxygen therapy (LTOT)
- Participants participating in, or scheduled for, an intensive (active) COPD rehabilitation program (participants who are in the maintenance phase of a rehabilitation program are eligible to take part)
- Concomitant medication restrictions: Oral anticoagulants, oral steroids (e.g. prednisone or Medrol), theophylline, chronic azithromycin, or roflumilast
- Have any other conditions, which, in the opinion of the Investigator would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study
Trial locations and contacts
15 sites in 4 countries.
15 sites in 4 countries
Germany7 sites
Pneumologisches Studienzentrum Markgrafenstrasse
Berlin, 10969
MECS Research GmbH
Berlin, 12203
Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH
Großhansdorf, 22927
Hamburger Institut far Therapieforschung GmbH
Hamburg, 20354
KLB Gesundheitsforschung Lubeck GmbH
Lübeck, 23552
IKF Pneumologie Mainz Helix Medical Excellence Center Mainz
Mainz, 55128
ZMS-Zentrum fur medizinische Studien GmbH
Warendorf, 48231
Czechia5 sites
MediTrial s.r.o.
Jindřichův Hradec, 37701
Plicni ambulance Kralupy
Kralupy nad Vltavou, 27801
CEFISPIRO s.r.o.
Lovosice, 410 02
Plicni Ambulance Rokycany, s.r.o.
Rokycany, 33701
PNEUMOLOGIE VARNSDORF s.r.o.
Varnsdorf, 40747
Hungary2 sites
Csongrad Megyei Mellkasi Betegsegek Szakkorhaza
Deszk, 6772
Selye Janos Korhaz, Rendelointezet
Komárom, 2900
United Kingdom1 site
Queen Anne Street Medical Centre, Heart Lung Center
London, Nw1 8HU
About this study
Official title: A Double-Blind, Placebo-Controlled, Phase 2a Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Patients With Mild to Moderate COPD With Chronic Bronchitis
The purpose of this study was to evaluate the effect of ION-827359 on forced expiratory volume in 1 second (FEV1) in participants with mild to moderate COPD with CB.
Read the detailed description
This was a multi-center, double-blind, placebo-controlled, randomized, Phase 2a study of ION-827359 in up to 180 participants. The participants were randomized to receive oral inhalation of either ION-827359 or placebo for up to 13 weeks. At the end of 13 weeks, participants entered a 10-week post-treatment evaluation period.
- Being tested
- ION-827359, Placebo
- Keywords
- Chronic Bronchitis, IONIS-ENaCRx
- Medical subject headings
- Bronchitis, Chronic, Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ION-827359Drug
ION-827359 administered by oral inhalation
PlaceboDrug
Placebo administered by oral inhalation
ION-827359Drug
ION-827359 administered by oral inhalation
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Single-dose of placebo was administered by oral inhalation via nebulizer, once every week for up to 13 weeks. Receives: Drug: Placebo |
| ION-827359 37.5 milligrams (mg) | Experimental | Single-dose of ION-827359 37.5 mg was administered by oral inhalation via nebulizer, once every week for up to 13 weeks. Receives: Drug: ION-827359 |
| ION-827359 75 mg | Experimental | Single-dose of ION-827359 75 mg was administered by oral inhalation via nebulizer, once every week for up to 13 weeks. Receives: Drug: ION-827359 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to the Primary Time Point in Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Baseline was defined as the last non-missing measurement prior to the first study drug administration. The primary time point was defined as the average of weeks 13 and 14. FAS=Full analysis set.
Measured: From Baseline up to average of Weeks 13 and 14
Secondary outcomes (11)
Change From Baseline in the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Respiratory Symptoms (E-RS) Daily Symptom Diary Total Score to the Primary Time Point
The E-RS scale is a participant-reported outcome (PRO) designed to measure the symptoms of participants with chronic obstructive pulmonary disease (COPD). The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation. The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness (comprised of 5 items, score range [0-17]), cough and sputum (comprised of 3 items, score range [0-11]), and chest symptoms (comprised of 3 items, score range [0-12]). The E-RS was collected on the daily e-diary. The total score was derived by summing the 11-item scores and ranged between 0 to 40 with higher values indicating severe respiratory symptoms. The primary time point was defined as the average of weeks 13 and 14.
Measured: From Baseline up to average of weeks 13 and 14
Change From Baseline in the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) to the Week 14 Time Point
The CAT is an eight-item questionnaire that was completed by the participant and is designed to quantify the impact of COPD symptoms on the health status of participants. Each item is rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score is calculated by summing the scores of all items and ranges from 0 to 40. Higher scores indicate a severe condition (more severe impact of COPD on a participant's life).
Measured: From Baseline to Week 14
Change From Baseline in St. George's Respiratory Questionnaire - COPD Specific (SGRQ-C) Total Score to the Week 14 Time Point
The SGRQ is a participant completed, a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in participants with obstructive airway disease. The shorter 40-item version (SGRQ-C) which does not specify a Recall Period and has been validated specifically for COPD participants was used in this study. It consists of 40 items each weighted from 0 to a possible maximum of 100. Items 1-7 produced the symptoms score, 9-12 the activity score, and items 8, 10, 11, 13 and 14 the impacts score. Each component sub-score was calculated as a percentage of the summed weights of each item out of the sum of the maximum possible weight for that component (range 0-100). The total score was calculated by summing the weights to all positive responses in each component, where a positive item indicated the presence of symptoms, expressed as a percentage (range 0-100). Higher scores indicated a worse outcome (more limitations)
Measured: From Baseline to Week 14
Change From Baseline in Post-Bronchodilator FEV1
Post-bronchodilator FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation after administration of bronchodilator. Baseline was defined as the last non-missing measurement prior to the first study drug administration.
Measured: From Baseline to end of treatment (EOT) [Up to Week 14]
Cmax: Maximum Observed Plasma Concentration for ION-827359
Measured: Days 1 and 85
Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359
Measured: Days 1 and 85
AUC[0-24h]: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours for ION-827359
Measured: Days 1 and 85
Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity
An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE is considered related to the medicinal (investigational) product. A TEAE is defined as any AE starting or getting worse on or after the first dose of the study drug. The severity of a TEAE was assessed by the investigator and classified into one of the following: mild, moderate, and severe.
Measured: Up to Week 24
Percentage of Participants With Clinically Significant Change in Laboratory Values
Laboratory parameters for serum chemistry, hematology, urinalysis, coagulation, complement, and lipids were assessed.
Measured: Up to Week 24
Percentage of Participants With Clinically Significant Change in Vital Sign Parameters
Vital signs included assessment of heart rate, blood pressure, respiratory rate, and temperature.
Measured: Up to Week 24
Percentage of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
ECG parameters of ventricular rate, PR interval, QRS duration, QT, or QTc were assessed.
Measured: Up to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2020
- Study start22 Dec 2020
- Primary completion27 Apr 2021
- Study completion9 Aug 2021
Why it stopped: Business Decision to Terminate Study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic BronchitisStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04441788
- Sponsor's protocol ID
- ION-827359-CS2
- Other IDs
- 2020-000210-15
- Status last verified
- Nov 2022
- First submitted
- 18 Jun 2020
- Last updated
- 20 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled, Phase 2a Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Patients With Mild to Moderate COPD With Chronic Bronchitis
- ClinicalTrials.gov ID
- NCT04441788
- Acronym / sponsor ID
- ION-827359-CS2
- Keywords
- Chronic Bronchitis, IONIS-ENaCRx
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Decision to Terminate Study
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Dec 2020 (actual)
- Primary completion
- 27 Apr 2021 (actual)
- Study completion
- 9 Aug 2021 (actual)
- First posted
- 22 Jun 2020 (actual)
- Results
- Posted 20 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to evaluate the effect of ION-827359 on forced expiratory volume in 1 second (FEV1) in participants with mild to moderate COPD with CB.
Detailed description
This was a multi-center, double-blind, placebo-controlled, randomized, Phase 2a study of ION-827359 in up to 180 participants. The participants were randomized to receive oral inhalation of either ION-827359 or placebo for up to 13 weeks. At the end of 13 weeks, participants entered a 10-week post-treatment evaluation period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboSingle-dose of placebo was administered by oral inhalation via nebulizer, once every week for up to 13 weeks. |
| ION-827359 37.5 milligrams (mg) | Experimental | Drug: ION-827359Single-dose of ION-827359 37.5 mg was administered by oral inhalation via nebulizer, once every week for up to 13 weeks. |
| ION-827359 75 mg | Experimental | Drug: ION-827359Single-dose of ION-827359 75 mg was administered by oral inhalation via nebulizer, once every week for up to 13 weeks. |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements
- Males or females. Aged 40-70 inclusive at the time of informed consent
- Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or postmenopausal
- BMI < 35.0 kg/m^2
- Participants with a diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS)
Key exclusion criteria (19 listed)
- Clinically significant abnormalities in medical history (e.g., previous acute coronary syndrome within 6 months of screening, congestive heart failure, major surgery within 3 months of Screening) or physical examination
- Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a subject unsuitable for inclusion
- Any active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to first day Study Drug product is administered to the participant (Study Day 1)
- Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
- Clinically important pulmonary disease other than COPD
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ION-827359ION-827359 administered by oral inhalation | Drug | ION-827359 37.5 milligrams (mg) |
| PlaceboPlacebo administered by oral inhalation | Drug | Placebo |
| ION-827359ION-827359 administered by oral inhalation | Drug | ION-827359 75 mg |
Primary outcome
Change From Baseline to the Primary Time Point in Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo
Time frame: From Baseline up to average of Weeks 13 and 14
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Baseline was defined as the last non-missing measurement prior to the first study drug administration. The primary time point was defined as the average of weeks 13 and 14. FAS=Full analysis set.
11 secondary outcomes
Change From Baseline in the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Respiratory Symptoms (E-RS) Daily Symptom Diary Total Score to the Primary Time Point
Time frame: From Baseline up to average of weeks 13 and 14
Change From Baseline in the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) to the Week 14 Time Point
Time frame: From Baseline to Week 14
Change From Baseline in St. George's Respiratory Questionnaire - COPD Specific (SGRQ-C) Total Score to the Week 14 Time Point
Time frame: From Baseline to Week 14
Change From Baseline in Post-Bronchodilator FEV1
Time frame: From Baseline to end of treatment (EOT) [Up to Week 14]
Cmax: Maximum Observed Plasma Concentration for ION-827359
Time frame: Days 1 and 85
Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359
Time frame: Days 1 and 85
AUC[0-24h]: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours for ION-827359
Time frame: Days 1 and 85
Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity
Time frame: Up to Week 24
Percentage of Participants With Clinically Significant Change in Laboratory Values
Time frame: Up to Week 24
Percentage of Participants With Clinically Significant Change in Vital Sign Parameters
Time frame: Up to Week 24
Percentage of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
Time frame: Up to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ION-827359 in people with Chronic Bronchitis and Chronic Obstructive Pulmonary Disease, run by Ionis Pharmaceuticals, Inc. at 15 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Germany, Czechia, Hungary, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to the Primary Time Point in Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo (time frame: From Baseline up to average of Weeks 13 and 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2022.